Phosphine compound, its intermediate, its complex with palladium and a manufacturing method of unsaturated compounds by using the palladium complex

ABSTRACT

Palladum-phosphine complexes obtained by reacting a 5 compound of formula (1) below with a palladium compound: F(I) (wherein R 1  is a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R 2  and R 3  are each, the same or different, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R 4  and R 5  are each, the same or different, a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl group which may be substituted; R 6 , R 7 , R 8  and R 9  are each, the same or different, an alkyl group, a cycloalkyl group, a phenyl group which may be substituted, an alkoxyl group, a dialkylamino group, a halogen atom, a phenyl group, a benzyl group, a naphthyl group or a halogenated alkyl group; R 6  and R 7 , R 8  and R 9  may be combined to form, each, a fused ring, a trimethylene group, a tetramethylene group or a 20 methylenedioxy group; p, q, r and s are each an integer of 0 to 5; and p+q, and r+s are each in the range of 0 to 5.), which is a novel and efficient catalyst for manufacturing various useful compounds.

TECHNICAL FIELD

The present invention relates to a phosphine compound, its intermediate,and a palladium-phosphine complex obtainable by treating the saidphosphine compound with a palladium compound. The present invention alsorelates to a manufacturing method of unsaturated compounds or aromaticcompounds by using the said palladium-phosphine complex as a catalyst.

BACKGROUND ART

At present many transition metal complexes have been used as catalystsfor organic synthetic reactions. It is well known that the ligand playsa very important role, together with the transition metals as thecentral metals, as a factor to make full use of the performance oractivity of those catalysts. Many phosphine compounds, for example, havebeen developed as the ligands and have had a key role as such.

The most important thing is to constitute an optimal catalyst for eachof the various kinds of reactions and substrates. However, thecombination of the central metal and the phosphine ligand, constitutingthe catalyst, is so complex that the known phosphine ligands may, insome cases, be insufficient without, for example, yielding enoughcatalytic activity for use in the practical industrial production. Thus,development of excellent novel phosphine ligands is still eagerlydesired.

DISCLOSURE OF INVENTION

Accordingly, the object of the present invention is to provide a novelligand useful for various catalytic reactions and to provide,furthermore, by using the catalysts which contain this ligand, a methodfor manufacturing unsaturated compounds which are important asintermediates of pharmaceuticals and organic electronic materials.

The present inventors have found, after an intensive study to solve theproblem mentioned above, that a novel phosphine compound with acyclopropane moiety is an excellent ligand and that the complex of thisnovel phosphine compound with a palladium compound is extremelyefficient as catalyst for the synthesis of unsaturated or aromaticcompounds, making it possible to manufacture efficiently unsaturated oraromatic compounds, particularly aromatic compounds, and completed thepresent invention. Furthermore, the present inventors have also found anovel intermediate for manufacturing the phosphine compound with acyclopropane skeleton mentioned above.

Thus the present invention includes the following:

1. a phosphine compound of formula (1),

wherein R¹ is a hydrogen atom, an alkyl group, a cycloalkyl group or aphenyl group which may be substituted; R² and R³ are each, the same ordifferent, an alkyl group, a cycloalkyl group or a phenyl group whichmay be substituted; R⁴ and R⁵ are each, the same or different, ahydrogen atom, an alkyl group, a cycloalkyl group or a phenyl groupwhich may be substituted; R⁶, R⁷, R⁸ and R⁹ are each, the same ordifferent, an alkyl group, a cycloalkyl group, a phenyl group which maybe substituted, an alkoxyl group, a dialkylamino group, a halogen atom,a benzyl group, a naphthyl group or a halogenated alkyl group; R⁶ andR⁷, or R⁸ and R⁹ each may be combined to form, a fused ring, atrimethylene group, a tetramethylene group or a methylenedioxy group; p,q, r and s are each an integer of from 0 to 5; and p+q, and r+s are eachin the range of from 0 to 5;

2. a palladium-phosphine complex which can be obtained by reacting thephosphine compound mentioned in 1 above with a palladium compound;

3. the palladium-phosphine complex mentioned in 2 above, wherein thepalladium compound is a palladium salt or a palladium complex in whichthe valency of palladium is 4, 2 or 0;

4. a manufacturing method of an unsaturated compound or an aromaticcompound by the use of palladium-phosphine complexes mentioned in 2 or 3above as a catalyst;

5. a manufacturing method of an unsaturated compound or an aromaticcompound by the use of the phosphine compound mentioned in 1 above and apalladium compound.

6. the manufacturing method mentioned in 4 or 5 above, which comprisesreacting a compound of formula (3) or (4) below,

wherein, in formula (3), Ar¹ is an aryl group which may be substitutedor a heteroaryl group which may be substituted; X¹ is a chlorine atom, abromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, amethanesulfonyloxy group or a para-toluenesulfonyloxy group and m¹ is aninteger of from 1 to 4, and,

-   -   in formula (4), R¹⁰¹, R¹¹¹ and R¹²¹ are each, the same or        different, a hydrogen atom, an alkyl group, an aryl group which        may be substituted, a heteroaryl group which may be substituted,        an alkoxycarbonyl group or a cyano group; X¹¹ is a chlorine        atom, a bromine atom, an iodine atom, a        trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or        a para-toluenesulfonyloxy group,        with a compound, of formula (5) or (6) below,        wherein, in formula (5), Ar² is an aryl group which may be        substituted or a heteroaryl group which may be substituted; X²        is B(OR¹³)(OR¹⁴), Sn(R¹⁵)₃, MgX, ZnX, Al(R¹⁵)₂ or Li, and,    -   in formula (6), R¹⁰, R¹¹ and R¹² are each, the same or        different, a hydrogen atom, an alkyl group, an aryl group which        may be substituted, a heteroaryl group which may be substituted,        an alkoxycarbonyl group or a cyano group; R¹⁰ and R¹² may be        combined to form a single bond, forming together with the        existing double bond a triple bond; X³ is a hydrogen atom,        B(OR¹³)(OR¹⁴), Sn(R¹⁵)₃, MgX, ZnX, Al(R¹⁵)₂ or Li; R¹³ and R¹⁴        are each, the same or different, a hydrogen atom, an alkyl        group, or, combined to form an ethylene group or a        1,2-dimethylethylene group; R¹⁵ is an alkyl group, and X is a        chlorine atom, a bromine atom or an iodine atom,        to give a compound of formula (7), (8), (9) or (10),        wherein Ar¹, Ar², R¹⁰, R¹¹, R¹², R¹⁰¹, R¹¹¹ and R¹²¹ are as        defined above and m² is an integer of 1 to 4;

7. a manufacturing method mentioned in 4 or 5 above, which comprisesreacting a compound of formula (3) or (4) below,

wherein, in formula (3), Ar¹ is an aryl group which may be substitutedor a heteroaryl group which may be substituted; X¹ is a chlorine atom, abromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, amethanesulfonyloxy group or a para-toluenesulfonyloxy group and m¹ is aninteger of from 1 to 4, and,

-   -   in formula (4), R¹⁰¹, R¹¹¹ and R¹²¹ are each, the same or        different, a hydrogen atom, an alkyl group, an aryl group which        may be substituted, a heteroaryl group which may be substituted,        an alkoxycarbonyl group or a cyano group; X¹¹ is a chlorine        atom, a bromine atom, an iodine atom, a        trifluoromethanesulfonyloxy group, a methanesulfonyloxy group or        a para-toluenesulfonyloxy group,        with an oxygen compound or nitrogen compound of formula (11)        below,        R^(16—QH)  (11)        wherein R¹⁶ is an alkyl group, an aryl group which may be        substituted, or a heteroaryl group which may be substituted; Q        is an oxygen atom,        wherein R¹⁷, R¹⁸ and R¹⁹ are each a hydrogen atom, an alkyl        group, an aryl group which may be substituted or a heteroaryl        group which may be substituted; and R¹⁶ and R¹⁷ may be combined        to form a divalent aromatic ring which may be substituted, to        give a compound of formula (12) or (13) below,        wherein Ar¹, Q, R¹⁶, R¹⁰¹, R¹¹¹, and R¹²¹ are as defined above        and m³ is an integer of 1 to 4.

8. the manufacturing method mentioned in 4 or 5 above, which comprisesreacting an aromatic compound of formula (3),Ar¹(X¹)_(m) ¹  (3)wherein Ar¹ is an aryl group which may be substituted or a heteroarylgroup which may be substituted; X¹ is a chlorine atom, a bromine atom,an iodine atom, a trifluoromethanesulfonyloxy group, amethanesulfonyloxy group or a para-toluenesulfonyloxy group, and m¹ isan integer of from 1 to 4,with a carbonyl compound or a cyano compound of formula (14),R¹⁸—CH₂—R¹⁹  (14)wherein R¹⁸ is a hydrogen atom, CO₂R²⁰, C(═O)R²¹ or a cyano group; R¹⁹is CO₂R²², C(═O)R²³ or a cyano group; R²⁰, R²¹, R²² and R²³ are each analkyl group, an aryl group which may be substituted or a heteroarylgroup which may be substituted,to give a compound of formula (15),

wherein Ar¹, R¹⁸ and R¹⁹ are as defined above and m⁴ is an integer of 1to 4.

9. the manufacturing method mentioned in 4 or 5 above, which comprisesreacting an aromatic compound of formula (3),Ar¹(X¹)m¹  (3)wherein Ar¹ is an aryl group which may be substituted or a heteroarylgroup which may be substituted; X¹ is a chlorine atom, a bromine atom,an iodine atom, a trifluoromethanesulfonyloxy group, amethanesulfonyloxy group or a para-toluenesulfonyloxy group; and m¹ isan integer of from 1 to 4, with carbon monoxide and an alcohol offormula (16),R²⁴OH  (16)wherein R²⁴ is an alkyl group,to give a carboxylic ester of formula (17),Ar¹(CO₂R²⁴)m⁵  (17)wherein Ar¹ and R²⁴ are as defined above and m⁵ is an integer of 1 to 4.

10. the manufacturing method of unsaturated compounds mentioned in anyone of 4 to 9 above, which comprises carrying out the reaction in thepresence of a base;

11. a halogeno compound of formula (2) below,

wherein R¹, R⁴ and R⁵ are each, the same or different, a hydrogen atom,an alkyl group, a cycloalkyl group or a phenyl group which may besubstituted; X⁴ is a halogen atom; R⁶, R⁷, R⁸ and R⁹ are each, the sameor different, an alkyl group, a cycloalkyl group or a phenyl group whichmay be substituted, an alkoxyl group, a dialkylamino group, a halogenatom, a phenyl group, a benzyl group, a naphthyl group or a halogenatedalkyl group; R⁶ and R⁷, and R⁸ and R⁹ each may be combined to form afused ring, a trimethylene group, a tetramethylene group or amethylenedioxy group; p, q, r and s are each an integer of from 0 to 5;and p+q, and r+s are each in the range of from 0 to 5.

In the present invention, an alkyl group means a linear or branchedalkyl group of from 1 to 30 carbon atoms, or more preferably, the one offrom 1 to 10 carbon atoms. Specific examples of such an alkyl group aremethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl,tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, n-hexyl,isohexyl, 2-ethylhexyl, n-heptyl, n-octyl, n-nonyl and n-decyl. Thesegroups may be substituted with cycloalkyl group(s) to be mentionedbelow.

In the present invention, a cycloalkyl group means a cycloalkyl group offrom 5 to 8 carbon atoms. Specific examples of such a cycloalkyl groupinclude cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Thesecycloalkyl groups may be substituted with the alkyl groups mentionedabove.

In the present invention, an alkoxy group means a linear or branchedalkoxy group of from 1 to 30 carbon atoms, or more preferably the one offrom 1 to 10 carbon atoms. Specific examples of such an alkoxy groupinclude methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy,sec-butoxy, tert-butoxy, n-pentyloxy, isopentyloxy, neopentyloxy,n-hexyloxy, isohexyloxy, 2-ethylhexyloxy, n-heptyloxy, n-octyloxy,n-nonyloxy and n-decyloxy.

In the present invention, an alkyl group of a dialkylamino group meansan alkyl group mentioned above, and the two alkyl groups may be the sameor different. Examples of such a dialkylamino group includedimethylamino, diethylamino, di(n-propyl)amino, diisopropylamino,di(n-butyl)amino, di(n-pentyl)amino and di(n-hexyl)amino.

In the present invention, halogen atoms include a fluorine atom, achlorine atom, a bromine atom, and an iodine atom.

In the present invention, a halogenated alkyl group means a group formedby replacing one of the hydrogen atoms of the alkyl groups mentionedabove with a halogen atom mentioned above, the preferable halogen atombeing a fluorine atom. Specific examples of such halogenated alkylgroups include perfluoroalkyl groups such as trifluoromethyl,pentafluoroethyl, heptafluoropropyl, etc. and fluoroalkyl such asdifluoromethyl and monofluoromethyl etc.

In the present invention, a phenyl group which may be substituted meansa phenyl group in which at least one of the hydrogen atoms on the saidphenyl group is substituted with substituent(s) or an unsubstitutedphenyl group. Examples of said substituent include an alkyl group, acycloalkyl group, an alkoxyl group, a dialkylamino group, a halogenatom, a phenyl group, a benzyl group, a naphthyl group and a halogenatedalkyl group, all of which are mentioned above.

The following is the description of the phosphine compounds of thepresent invention.

In the phosphine compounds of formula (1) of the present invention, R¹is a hydrogen atom, an alkyl group, a cycloalkyl group or a phenyl groupwhich may be substituted, and specific examples of such alkyl groups,cycloalkyl groups, and phenyl groups which may be substituted includethose mentioned above;

-   -   R² and R³ are each, the same or different, an alkyl group, a        cycloalkyl group or a phenyl group which may be substituted, and        specific examples of such alkyl groups, cycloalkyl groups, and        phenyl groups which may be substituted include those mentioned        above;    -   R⁴ and R⁵ are each, the same or different, a hydrogen atom, an        alkyl group, a cycloalkyl group or a phenyl group which may be        substituted, and specific examples of such alkyl groups,        cycloalkyl groups, and phenyl groups which may be substituted        include those mentioned above.

R⁶, R⁷, R⁸ and R⁹ are each, the same or different, a hydrogen atom, analkyl group, a cycloalkyl group or a phenyl group which may besubstituted, an alkoxyl group, a dialkylamino group, a halogen atom,benzyl group, naphthyl group, and a halogenated alkyl group, andspecific examples of such alkyl groups, cycloalkyl groups, phenyl groupswhich may be substituted, alkoxyl groups, dialkylamino groups, halogenatoms and halogenated alkyl groups include those mentioned above.

R⁶ and R⁷, R⁸ and R⁹ each may be combined together to form a fused ring,a trimethylene group, a tetramethylene group and a methylenedioxy group.Examples of said fused ring include a naphthalene ring, an anthracenering, a phenanthrene ring, a benzofuran ring, a benzothiophene ring, anindole ring and a quinoline ring, which are formed by condensation ofR⁶, R⁷, R⁸ and R⁹ with the phenyl group on which they are present.

The phosphine compounds of formula (1) of the present invention canspecifically be manufactured, for example, by the method shown below,but the present invention is not restricted by this method:

wherein Hal is chlorine or bromine, and Ph is phenyl.

One of the phosphine compounds of the present invention,2,2-diphenyl-1-(diphenylphosphino)-1-methylcyclopropane, can bemanufactured by reacting monobromocyclopropane compound (C) ormonochlorocyclopropane compound (C) with magnesium metal to give acyclopropylmagnesium halide and then by reacting the latter compoundwith diphenylphosphine chloride in the presence of copper iodide. Themonobromocyclopropane compound (C) can, in turn, be prepared by allowingdibromocyclopropane compound (B), obtainable by the reaction of1,1-diphenylethylene (A) with potassium tert-butoxide and bromoform, toreact with n-butyllithium and methyl iodide. Alternatively,1,1-diphenylethylene is reacted with 1,1-dichloroethane andn-butyllithium to give the monochlorocyclopropane compound (C).

Diarylmonohalogenocyclopropane compounds (C), the intermediates to thephosphine compounds of the present invention in the process shown above,are useful intermediates for the preparation of the phosphine compoundsof the present invention. Namely, the phosphine compounds of the presentinvention are conveniently manufactured by reacting thesediarylmonohalogenocyclopropane compounds (C) with lithium metal,alkyllithium or magnesium metal to give cyclopropyllithium derivativesor cyclopropylmagnesium halide derivatives, which are then reacted withvarious chlorophosphine derivatives.

The following is the more detailed description of the manufacturingmethods of the phosphine compounds and the intermediatemonohalogenocyclopropane compounds of the present invention.

In the process for manufacturing the phosphine compounds of the presentinvention mentioned above, diaryldihalogenocyclopropanes (B) can beobtained by reacting diarylethylenes (A) with haloforms in the presenceof bases.

The amount used of the haloform is preferably from about 0.1 to 10 timesor especially preferably from about 0.5 to 4 times that ofdiarylethylene (A) in moles.

Specific examples of the reaction solvent include hydrocarbons such aspentane, hexane, heptane, etc.; aromatic hydrocarbons such as benzene,toluene, xylene, etc.; and ethers such as diethyl ether,tetrahydrofuran, dioxane, etc. Among them, hydrocarbons such as pentane,hexane, heptane, etc. are preferably used. The amount of the solventused is from about 0.2 to 30 times, or especially preferably from about0.5 to 10 times that of the diarylethylene (A) in volume.

The reaction is usually carried out in an atmosphere of inert gases suchas nitrogen, argon, etc. The reaction time is usually from 10 minutes toabout 30 hours, or more preferably from 30 minutes to about 16 hours.The reaction is usually complete at the temperatures of from −80 toabout 100° C., or more preferably from −20 to about 60° C., althoughthese reaction conditions may be altered appropriately depending on thekind and amounts of the diarylethylene (A) and haloform used.

After completion of the reaction, the reaction mixture is worked-up asusual giving the objective compound.

In the process shown above, the diarylmonohalogenocyclopropanes (C) canbe obtained by reacting diaryldihalogenocyclopropanes (B) with halidesor dialkyl sulfate in the presence of an organometallic compound such asan organolithium compound.

Specific examples of the organolithium compound include methyllithium,ethyllithium, n-propyllithium, n-butyllithium, sec-butyllithium,tert-butyllithium and phenyllithium. Among them, n-butyllithium,sec-butyllithium, and tert-butyllithium are more preferably used. Theamount of the organolithium compound used is preferably from about 0.4to 3.0 times, and especially preferably from about 0.8 to 1.5 times thatof the diaryldihalogenocyclopropane (B) used in moles.

Specific examples of the reaction solvent include ethers such asdiethylether, tetrahydrofuran, dioxane, diisopropylether,dimethoxyethane, etc., among which diethylether and tetrahydrofuran aremore preferably used. The amount of the solvent used is preferably fromabout 1.0 to 50 times, or especially preferably from about 2.0 to 25times that of the diarylethylene (A) used in volume.

The reaction is usually carried out in an atmosphere of inert gases suchas nitrogen, argon, etc. and the reaction time is usually from 10minutes to about 40 hours, or more preferably from 30 minutes to about18 hours, and the reaction temperature is usually from −120 to about100° C., or more preferably from −80 to about 60° C., although thesereaction conditions may be altered appropriately depending on the kindand amount of the diaryldihalogenocyclopropanes (B) and halogenidesused.

After completion of the reaction, the reaction mixture is worked-up asusual giving the objective compound.

Furthermore, in the process shown above, thediarylmonohalogenocyclopropanes (C) can be obtained by reactingdiarylethylenes (A) with dihalogenides (for example, 1,1-dichloroethaneand 1,1-dibromoethane.) in the presence of an organometallic compoundsuch as an organolithium compound, etc.

Specific examples of the organolithium compounds include methyllithium,ethyllithium, n-propyllithium, n-butyllithium, sec-butyllithium,tert-butyllithium and phenyllithium. Among them, n-butyllithium,sec-butyllithium and tert-butyllithium are more preferably used. And,the amount of the organolithium compound used is preferably from about0.4 to 20 times and especially preferably from about 0.8 to 10 timesthat of the diarylethylene compound (A) used in moles.

Specific examples of the reaction solvent include ethers such as diethylether, tetrahydrofuran, dioxane, diisopropyl ether and dimethoxyethane,among which diethyl ether and tetrahydrofuran are more preferably used.The amount of the solvent used is preferably from about 1.0 to 50 timesand especially preferably from about 2.0 to 25 times that of thediarylethylene (A) used in volume.

The reaction is usually carried out in an atmosphere of inert gases suchas nitrogen, argon, etc., and the reaction time is usually from 10minutes to about 40 hours, or more preferably from 30 minutes to about18 hours, and the reaction temperature is usually from −120 to about120° C., or more preferably at from −80 to about 60° C., although thesereaction conditions may be altered appropriately depending on the kindand amount of the diaryldihalogenocyclopropanes (B) and dihalogenidesused.

After completion of the reaction, the reaction mixture is worked-up asusual to give the objective compound.

The phosphine compounds (D) of the present invention are obtained,according to the procedure shown above, by reactingdiarylmonohalogenocyclopropanes (C) with metal such as lithium andmagnesium to give cyclopropyllithium compounds and cyclopropylmagnesiumhalides, respectively, followed by the reacting of those organometalliccompounds with chlorophosphines.

Specific examples of the metal which can be used include lithium andmagnesium. In cases where lithium is used, the amount of lithium used ispreferably from about 1.0 to 3.0 times or especially preferably fromabout 1.5 to 2.5 times that of the substrate,diarylmonohalogenocyclopropanes (C), used in moles.

And, in cases where magnesium is used, the amount of magnesium used ispreferably from about 1.0 to 3.0 times or especially preferably fromabout 1.2 to 1.5 times that of the substrate,diarylmonohalogenocyclopropanes (C), used in moles.

Specific examples of the reaction solvent include ethers such as diethylether, tetrahydrofuran, dioxane, diisopropyl ether and dimethoxyethane,among which diethyl ether and tetrahydrofuran are more preferably used.The amount of the solvent used is preferably from about 1.0 to 50 timesand especially preferably from about 2.0 to 25 times that of thediarylmonohalogenocyclopropanes (C) used in volume.

The reaction is usually carried out in an atmosphere of inert gases suchas nitrogen, argon, etc. The reaction time is usually from 10 minutes toabout 40 hours, or more preferably from 30 minutes to about 18 hours,and the reaction temperature is usually from −120 to about 120° C., ormore preferably from −80 to about 80° C., although these reactionconditions may be altered appropriately depending on the kind and amountused of the diarylmonohalogenocyclopropanes (C) and chlorophosphines.

After completion of the reaction, the reaction mixture is worked-up asusual giving the objective compound.

The phosphine compounds of formula (1) of the present invention thusobtained form, as ligands, palladium-phosphine complexes with palladiumcompounds.

The palladum-phosphine complexes obtainable by reacting the phosphinecompounds of formula (1) of the present invention with palladiumcompounds can be prepared by reacting the phosphine compounds of thepresent invention with π-allylpalladium chloride dimer(II) or withtris(dibenzylidene)dipalladium(0) according to the methods described inthe literature: for example, Y. Uozumi and T. Hayashi, J. Am. Chem.Soc., (1991), vol. 113, 9887; Gregory C. Fu, et al., J. Am. Chem. Soc.,(2001), vol. 123, 2719.

Specific examples of the palladium compounds which can be used includepalladium(IV) compounds such as sodium hexachloropalladate(IV)tetrahydrate, potassium hexachloropalladate(IV), etc., palladium(II)compounds such as palladium chloride(II), palladium bromide(II),palladium acetate(II), palladium(II) acetylacetonate,dichlorobis(benzonitrile)palladium(II),dichlorobis(acetonitrile)palladium(II),dichlorotetraamminepalladium(II),dichloro(cycloocta-1,5-diene)palladium(II), palladiumtrifluoroacetate(II) and π-allylpalladium chloride dimer, etc., andpalladium(0) compounds such as tris(dibenzylideneacetone)dipalladium(0),tris(dibenzylideneacetone)dipalladium-chloroform adduct(0), etc. Amongthem, dichlorobis(benzonitrile)palladium(II), π-allylpailadium chloridedimer(II), tris(dibenzylideneacetone)dipalladium(0) andtris(dibenzylideneacetone)dipalladium-chloroform adduct(0) are morepreferably used. The amount of the palladium compound used is preferablyfrom about 0.1 to 8.0 times, and especially preferably from about 0.2 to4.0 times that of the phosphine compound used in moles.

The reaction solvent is not limited to a special one, but any solventcan be used unless it does not inhibit the reaction severely. Examplesof such solvents include aliphatic organic solvents such as pentane,hexane, heptane, octane, etc.; alicyclic organic solvents such ascyclohexane, methylcyclohexane, etc.; aromatic organic solvents such asbenzene, toluene, xylene, etc.; ethers such as diethyl ether,diisopropyl ether, dimethoxyethane, tetrahydrofuran, dioxane, dioxolane,etc.; acetonitrile; dimethylformamide; dimethyl sulfoxide; andhexamethylphosphoric triamide.

Among them, aromatic organic solvents such as benzene, toluene, xylene,etc., and ethers such as diethyl ether, dimethoxyethane,tetrahydrofuran, dioxane, etc. are more preferably used. The amount ofthe solvent used is preferably from about 1.0 to 50 times, andespecially preferably from about 2.0 to 25 times that of the phosphinecompound used in volume.

The reaction is usually carried out in an atmosphere of inert gases suchas nitrogen, argon, etc. The reaction time is usually from 10 minutes toabout 40 hours, or more preferably from 30 minutes to about 18 hours,and the reaction temperature is usually from −20 to about 160° C., ormore preferably from 0 to about 120° C., although these reactionconditions may be altered appropriately depending on the kind and amountof the phosphine compounds used and the palladium compounds used.

After completion of the reaction, the reaction mixture is worked-up asusual giving the objective compound.

The palladium-phosphine complexes obtainable by the reaction of thephosphine compounds of the present invention with palladium compoundscan be used as catalysts in carbon to carbon bond-forming reactions incompounds having unsaturated bonds (for example, Suzuki couplingreaction, Stille coupling reaction, Negishi coupling reaction,Sonogashira coupling reaction, α-arylation of carbonyl compounds,alkoxycarbonylation, etc.), carbon to nitrogen bond-forming reactions(for example, arylamination reaction, vinylamination reaction, etc.),and carbon to oxygen bond-forming reactions (for examplearyletherification reaction, vinyletherification reaction, etc.).

According to the present invention, an unsaturated compound or anaromatic compound can be produced advantageously by the use of thepalladium-phosphine complex or alternatively by the use of the phosphinecompound and the palladium compound.

One of the manufacturing methods of the present invention is selectedfrom the reactions below:

(Hetero)aryl compounds of formula (3) which can be used in the presentinvention include (hetero)aryl bromides, (hetero)aryl chlorides,(hetero)aryl iodides, (hetero)aryltrifluoromethane sulfonates,(hetero)arylmethane sulfonates, (hetero)aryl para-toluenesulfonates and(hetero)aryl compounds having 1-4 halogen atoms or sulfonate moieties.

Specific examples of the (hetero)aryl compounds include aryl bromidessuch as bromobenzene, 1,4-dibromobenzene, 1,3,5-tribromobenzene,p-bromoanisole, p-bromotoluene, o-bromophenol, p-bromophenol,2-bromobenzotrifluoride, 4-bromobenzotrifluoride, mesityl bromide,4-bromophenethyl alcohol, 2-bromo-m-xylene, 2-bromo-p-xylene,5-bromo-m-xylene, 1-bromo-4-(trifluoromethoxy)benzene, 2-bromobiphenyl,4-bromobiphenyl, 4-bromo-1,2-(methylenedioxy)benzene,1-bromonaphthalene, 2-bromonaphthalene, 1-bromo-2-methylnaphthalene,1-bromo-4-methylnaphthalene, 1,4-dibromonaphthalene,4,4′-dibromobiphenyl, 2-bromothiophene, 2-bromopyridine,9-bromophenanthrene, 2-bromofuran, 2,4-difluorobromobenzene,2,4-di(trifluoromethyl)bromobenzene, 4-bromodimethylaminobenzene,4-bromobenzonitrile, tetrabromoperylene, dibromoanthanthrone, etc.; andthose compounds which are formed by replacing the bromine atom(s) in thearyl bromides mentioned above with chlorine or iodine atom(s).

Examples of the sulfonates include those compounds which are formed byreplacing the bromine atom in the bromide mentioned above with either atrifluoromethanesulfonyloxy group, a methanesulfonyloxy group or apara-toluenesulfonyloxy group. These sulfonates can be readily obtainedby treating the precursor phenols with sulfonylating agents such as, forexample, trifluoromethanesulfonic anhydride, methanesulfonyl chloride,etc. in the presence of bases such as triethylamine, etc.

Unsaturated compounds represented by formula (4) in the presentinvention include those compounds having a double bond formed between acarbon atom carrying a substituent X¹¹ which serves as the leaving groupin the reaction, and a carbon atom adjacent to it, such as, for example,vinyl halogenides, vinyl sulfonates and their analogs. Typical examplesof the bromides as such vinyl halogenides and their analogs includebromoethylene, 1-bromopropene, 2-bromopropene, 2-bromo-2-butene,1-bromo-1-butene, 1-bromo-2-butene, bromocyclopentene, bromocyclohexene,α-bromostylene, β-bromostylene, 2,2-diphenyl-1-bromoethylene,1,2-diphenylbromoethylene, 3-bromo-2-propen-1-ol, 2-bromo-2-propen-1-ol,methyl 2-bromoacrylate and 2-bromoacrylonitrile.

Examples of the sulfonates and their analogs include, takingtrifluoromethanesulfonates as representatives,trifluoromethanesulfonyloxyethylene,1-trifluoromethanesulfonyloxypropene,2-trifluoromethanesulfonyloxypropene,trifluoromethanesulfonyloxycyclopentene,trifluoromethanesulfonyloxycyclohexene and1-trifluoromethanesulfonyloxy-1-methoxyethylene.

(Hetero)aryl compounds of formula (5), which can be used in the presentinvention, include boronic acids, boronic esters, trialkylaryltincompounds, arylmagnesium halides, arylzinc halides, dialkylarylaluminiumcompounds and aryllithium compounds.

Although there is no particular limitation for the boronic acids,examples of the boronic acids include boronic acids such asphenylboronic acid, 4-methylphenylboronic acid, 2-thienylboronic acid,2-furylboronic acid, 2-pyridylboronic acid,2,3,4,5,6-pentafluorophenylboronic acid, 2-fluorophenylboronic acid,4-chlorophenylboronic acid, 2-bromophenylboronic acid,4-iodophenylboronic acid, 2,4-difluorophenylboronic acid,4-trifluoromethylphenylboronic acid, 3-cyanophenylboronic acid,4-formylphenylboronic acid, 4-methoxyphenylboronic acid,1-naphthylboronic acid, ferrocenylboronic acid, 4-hydroxyphenylboronicacid, etc., and esters (for example, dimethyl ester, diethyl ester,dipropyl ester and pinacol ester, etc.) of those arylboronic acidsmentioned above.

Although there is no particular limitation for the trialkyltincompounds, examples of the trialkyltin compounds includephenyltrimethyltin, phenyltriethyltin, phenyltributyltin,2-methylphenyltributyltin, 2,4,6-trimethylphenyltributyltin,4-methoxyphenyltributyltin, 2-pyridyltributyltin, 3-pyridyltributyltin,2-thienyltributyltin, 3-thienyltributyltin and 2-furyltributyltin.

Although there is no particular limitation for the arylmagnesiumhalides, arylzinc halides, dialkylarylaluminum compounds and aryllithiumcompounds, examples of said compounds are those such as phenylmagnesiumhalide, 4-biphenylmagnesium halide, 2-biphenylmagnesium halide,4-methoxyphenylmagnesium halide, 4-methylphenylmagnesium halide,3-methoxyphenylmagnesium halide, 3-methylphenylmagnesium halide,2-methoxyphenylmagnesium halide, 2-methylphenylmagnesium halide,2-pyridylmagnesium halide, 2-thienylmagnesium halide, 2-furylmagnesiumhalide, phenylzinc halide, 4-biphenylzinc halide, 2-biphenylzinc halide,2-methylphenylzinc halide, 3-methylphenylzinc halide, 4-methylphenylzinchalide, 2,6-dimethylphenylzinc halide, 2,4,6-trimethylphenylzinchalides, 4-methoxyphenylzinc halides, 2-pyridylzinc halides,3-pyridylzinc halides, 2-thienylzinc halides, 2-furylzinc halides,phenyldimethylaluminum, phenyldiethylaluminum, phenyldipropylaluminum,phenyldiisopropylaluminum, phenyldibutylaluminum,phenyldiisobutylaluminum, 2-methylphenyldiethylalluminum,4-methoxyphenyldiethylaluminum, 2-thienyldiethylaluminum, phenyllithium,2-methylphenyllithium, 4-methoxyphenyllithium, 2-thienyllithium,2-pyridyllithium, 2-furyllithium, etc.

Unsaturated compounds of formula (6) include olefins which may besubstituted, terminal acetylene compounds which may be substituted,acrylic acid esters and acrylonitriles which may be substituted on theα- or β-position, (hetero)aryl compounds which have a vinyl group andmay have additional substituent (s), alkenyl boronic acids, alkenylboronic acid esters, trialkylalkenyltin compounds, alkenylmagnesiumhalides, alkenylzinc halides, dialkylalkenylaluminum compounds andaklenyllithium compounds.

Specific examples of the olefins which may be substituted includeethylene, propene, 1-butene, 2-butene, 1-heptene, 2-heptene,cyclopentene, cyclohexene, methylcyclohexene, allyl alcohol, methacrylalcohol, homoallyl alcohol, crotyl alcohol, crotonaldehyde, vinyl butylether and allylbenzene.

Although there is no particular limitation for the acrylic acid estersand acrylonitriles which may be substituted on the α- or β-position,examples of such groups include methyl acrylate, ethyl acrylate, butylacrylate, tert-butyl acrylate, ethyl methacrylate, ethyl crotonate,acrylonitrile, methacrylonitrile and crotononitrile.

Although there is no particular limitation for the (hetero) arylcompounds which have a vinyl group and may have additionalsubstituent(s), examples as such group include styrene, stilbene,4-methylstyrene, 3-methylstyrene, 4-vinylmethoxybenzene,β-methoxystyrene, α-methylstyrene, 2-vinylthiophene, 3-vinylthiophene,2-vinylpyridine and 2-vinylfuran.

Although there is no particular limitation for the alkenylboronic acids,examples of such group include bononic acids such as vinylboronic acid,1-propen-1-ylboronic acid, 1-propen-2-ylboronic acid,1-buten-1-ylboronic acid, 1-buten-2-ylboronic acid, 2-buten-2-ylboronicacid, 1-penten-1-ylboronic acid, α-styrylboronic acid, β-styrylboronicacid, 1,2-diphenylethenylboronic acid, 2,2-diphenylethenylboronic acid,cyclopentenylboronic acid, cyclohexenylboronic acid,2-methylcyclohexenylboronic acid, etc. and their esters (for example,dimethyl esters, diethyl esters, dipropyl esters, pinacol esters, etc.)of those alkenylboronic acids.

Although there is no particular limitation for the trialkylalkenyltincompounds, examples of such compounds include vinyltrimethyltin,vinyltriethyltin, vinyltripropyltin, vinyltributyltin,1-propen-1-yltributyltin, 1-buten-1-yltributyltin,1-ethoxyethenyltributyltin, α-styryltributyltin, β-styryltributyltin,1,2-diphenylethenyltributyltin, 2,2-diphenylethenyltributyltin,cyclopentenyltributyltin, cyclohexenyltributyltin.

Although there is no particular limitation for the alkenylmagnesiumhalides, alkenylzinc halides, dialkylalkenylaluminum compounds andalkenyllithium compounds, examples of such groups include compounds suchas vinylmagnesium halides, 1-propen-1-ylmagnesium halides,1-propen-2-ylmagnesium halides, 1-buten-1-ylmagnesium halides,α-styrylmagnesiumhalides, β-styrylmagnesium halides,1,2-diphenylethenylmagnesium halides,2,2-diphenylethenylmagnesiumhalides, cyclopentenylmagnesium halides,cyclohexenylmagnesium halides, vinylzinc halides, 1-propen-1-ylzinchalides, 1-propen-2-ylzinc halides, 1-buten-1-ylzinc halides,α-stylylzinc halides, β-stylylzinc halides, 1,2-diphenylethenylmagnesiumhalides, 2,2-diphenylethenylmagnesium halides, cyclopentenylzinchalides, cyclohexenylzinc halides, vinyldimethylaluminum,vinyldiethylaluminum, vinyldipropylaluminum, vinyldiisopropylaluminum,vinyldibutylaluminum, vinyldiisobutylaluminum,1-propen-1-yldiethylaluminum, β-styryldiethylaluminum, vinyllithium,1-propen-1-yllithium, β-styryllithium, cyclopentenyllithium,cyclohexenyllithium, etc.

Although there is no particular limitation for the terminal acetylenecompounds which may be substituted, examples of such compounds includeacetylene, propyne, 1-butyne, 1-pentyne, 1-hexyne, 1-heptyne, 1-octyne,phenylacetylene, 2-propyn-1-ol, 3-butyn-1-ol, 2-methyl-3-butyn-2-ol,1-ethynylcyclohexanol and trimethylsilylacetylene.

In this manufacturing method, it is only required that not less than 1mole of the boronic acids, trialkylaryltin compounds, arylmagnesiumhalides, arylzinc halides, dialkylarylaluminum compounds and aryllithiumcompounds exist in the reaction system per 1 mole of the aromaticcompound (3) or the unsaturated compound (4). It is more preferable,however, that those compounds exist in the reaction system in an amountof 1 to 10 times that of the aromatic compound (3) or the unsaturatedcompound (4) in moles, because recovery of the unchanged material:boronic acids, trialkylaryltin compounds, arylmagnesium halides,arylzinc halides, dialkylarylaluminum compounds and aryllithiumcompounds, becomes complicated.

In this manufacturing method, it is only required that not less than 1mole of the terminal acetylene compounds which may be substituted, theacrylic esters which may be substituted on the α- or β-position and the(hetero)aryl compounds and acrylonitriles which have a vinyl group andmay have additional substituent(s) exist in the reaction system per 1mole of the aromatic compound (3) or the unsaturated compound (4). It ismore preferable, however, that those compounds exist in the reactionsystem in an amount of 1 to 10 times that of the aromatic compound (3)or the unsaturated compound (4) in moles, because recovery of theunchanged material including terminal acetylene compounds which may besubstituted, acrylic esters which may be substituted on the α- orβ-position, and (hetero)aryl compounds and acrylonitriles which have avinyl group and may have additional substituent(s), becomes complicated.

In this manufacturing method, it is appropriate to use bases asauxiliary agents. The bases to be used can be selected from inorganicand/or organic bases without being specifically restricted to thosecited. Examples of such bases are carbonates of alkali metals oralkaline earth metals such as lithium carbonate, sodium carbonate,potassium carbonate, rubidium carbonate, cesium carbonate, magnesiumcarbonate, calcium carbonate, barium carbonate, etc.; alkali metalalkoxides such as sodium methoxide, sodium ethoxide, sodium phenoxide,sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassiumphenoxide, potassium tert-butoxide, lithium methoxide, lithium ethoxide,lithium phenoxide, lithium tert-butoxide, etc.; hydroxides of alkalimetals or alkaline earth metals such as sodium hydroxide, potassiumhydroxide, lithium hydroxide, barium hydroxide, etc.; phosphates ofalkali metals such as lithium phosphate, potassium phosphate, sodiumphosphate, etc.; amines such as trimethylamine, triethylamine,triisopropylamine, tricyclohexylamine, diethylamine, diisopropylamine,methylmorpholine, pyridine and picoline; and alkali metal fluorides suchas lithium fluoride, potassium fluoride, sodium fluoride, cesiumfluoride, rubidium fluoride, etc.

The amount of the base used is preferably not less than 1 mole per 1mole of the aromatic compound (3) or the unsaturated compound (4). Withless than 1 mole equivalent of the base, the yield of the unsaturatedcompound obtained by the method of the present invention may be reduced.Although addition of even a large excess amount of the base hardlyaffects adversely on the yield of the unsaturated compound obtained, butit complicates the work-up procedure after completion of the reaction.Thus, the amount of the base used is more preferably in the range offrom 1 to 5 times in moles.

The methods mentioned above for manufacturing unsaturated compounds areusually carried out in the presence of a solvent inert to the reactions.The solvents which can be used are not restricted to any specific onesso long as they do not inhibit the reactions extremely, but includealiphatic organic solvents such as pentane, hexane, heptane, octane,etc.; alicyclic organic solvents such as cyclohexane, methylcyclohexane,etc.; aromatic organic solvents such as benzene, toluene, xylene, etc.;ethers such as diethyl ether, diisopropyl ether, dimethoxyethane,tetrahydrofuran, dioxane, dioxolane, etc.; acetonitrile;dimethylformamide; dimethylsulfoxide; hexamethylphosphotriamide, etc.Among these solvents, aromatic organic solvents such as benzene,toluene, xylene, etc., and ethers such as diethyl ether,dimethoxyethane, tetrahydrofuran, dioxane, etc. are used morepreferably.

The present invention can be carried out in an atmosphere of inert gasessuch as nitrogen, argon, etc., under normal pressure or under increasedpressure.

The present invention can be carried out at temperatures in the rangefrom about 0° C. to 300° C., or more preferably at temperatures in therange from about 20° C. to 200° C.

The reaction time of the present invention varies depending on the kindof the reaction and the reaction temperature, but can be selected from arange from about several minutes to 72 hours.

After completion of the reaction, the reaction mixture is treated by theordinary methods to give the objective compound.

A further manufacturing method of the present invention is the oneselected from the reactions below:

Thus, an aromatic compound (3) or an unsaturated compound (4) is reactedwith an oxygen or a nitrogen compound (11) in the presence of a base byusing the palladium-phosphine complex of the present invention or byusing pallasium compound and phosphine compound of the present inventionas catalyst to give a compound (12): an aromatic ether or an aromaticnitrogen compound, and a compound (13): an alkenyl ether or alkenylnitrogen compound.

Examples of the (hetero)aryl compound represented by formula (3) and theunsaturated compounds represented by formula (4) used in the presentinvention, include the same ones as those mentioned above.

Examples of the oxygen compound of formula (11) used in the presentinvention include alcohols which may be substituted, phenols which maybe substituted and heterocyclic compounds which have hydroxyl group(s)and may further be substituted, and examples of the nitrogen compound offormula (11) used in the present invention include primary amines,secondary amines, amides, imines, (di)alkylamines which may besubstituted, (di)arylalkylamines which may be substituted,(di)heteroarylamines which may be substituted, alkylarylamines which maybe substituted, alkylheteroarylamines which may be substituted, andamides and imines which may be substituted.

Specific examples of the oxygen compound include the followings: namely,phenol, 2-methoxyphenol, 2-tert-butylphenol, 2-methylphenol,2-dimethylaminophenol, 3-methoxyphenol, 3-tert-butylphenol,3-methylphenol, 3-dimethylaminophenol, 4-methoxyphenol,4-tert-butylphenol, 4-methylphenol, 4-dimethylaminophenol, 1-naphthol,2-biphenol, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol,2-butanol, and tert-butanol, although they are not restricted to thosecited.

Although specific examples of the nitrogen compounds are shown below,they are not limited thereto. As primary amines, there are exemplifiedby aliphatic primary amines such as ethylamine, propylamine, butylamine,isobutylamine, tert-butylamine, pentylamine, cyclopentylamine,hexylamine, cyclohexylamine, heptylamine, octylamine, etc., and aromaticprimary amines such as aniline, m-fluoroaniline, p-fluoroanline,o-anisidine, m-anisidine, o-toluidine, m-toluidine, p-toluidine,2-naphthylamine, 2-aminobiphenyl, 4-aminobiphenyl,3,4-methylenedioxyaniline, m-xylidine, p-xylidine, m-phenylenediamine,etc.

Although there is no particular limitation for the secondary amines,they include, for example, cyclic secondary amines such as piperazine,2-methylpiperazine, homopiperazine, N-methylhomopiperazine,2,6-dmethylpiperazine, N-methylpiperazine, N-ethylpiperazine,N-ethoxycarbonylpiperazine, N-benzylpiperazine, morpholine,2,6-dilmethylmorpholine, piperidine, 2,6-dimethylpiperidine,3,3-dimethylpiperidine, 3,5-dimethylpiperidine, 2-ethylpiperidine,4-piperidone, pyrrolidine, 2,5-dimethylpyrrolidine, carbazole, indole,indoline, acridone, quinacridone, etc., and acyclic secondary aminessuch as dimethylamine, diethylamine, and N-methylaniline, N-ethylanilne,N-methylbenzylamine, N-methylphenethylamine and diphenylaminederivatives which may be further substituted on the aromatic ring.

Although there is no particular limitation for the imines, they include,for example, benzophenone imine, 4,4′-dimethoxybenzophenone imine, etc.;

Although there is no particular limitation for the amides, they include,for example, 2-azetidinone (β-propiolactam), γ-butyrolactam,δ-valerolactam, ε-caprolactam, acetamide, propionamide,cyclohexylcarboxamide, benzamide, N-methylformamide, N-methylacetamide,N-ethylacetamide, N-methylcyclohexylcarboxamide, N-methylbenzamide, etc.

In this manufacturing method, the oxygen or nitrogen compound (11) is tobe present in the reaction system in the range of not less than 1 moleper 1 mole of the aromatic compound (3) or the unsaturated compound (4).It is more preferable, however, for the oxygen or nitrogen compound toexist in the reaction system in the range of 1 to 2 moles per 1 mole ofthe aromatic compound (3) or the unsaturated compound (4), becauserecovery of the unreacted oxygen or nitrogen compound (11) which becomescomplicated.

In the manufacturing method of the present invention, it is preferableto use bases as auxiliary agents. Such bases to be used can be selectedfrom inorganic bases and/or organic bases and are not restricted tospecific ones. Thus, examples of bases used preferably includecarbonates of alkali metals or alkaline earth metals such as lithiumcarbonate, sodium carbonate, potassium carbonate, rubidium carbonate,cesium carbonate, magnesium carbonate, calcium carbonate, bariumcarbonate, etc.; alkoxides of alkali metals such as sodium methoxide,sodium ethoxide, sodium phenoxide, sodium tert-butoxide, potassiummethoxide, potassium ethoxide, potassium phenoxide, potassiumtert-butoxde, lithium methoxide, lithium ethoxide, lithium phenoxide,lithium tert-butoxide, etc.; phosphates of alkali metals such as lithiumphosphate, potassiumphosphate, sodium phosphate, etc.

The amount of the base used is preferably not less than 1 mole per 1mole of the aromatic compound (3) or the unsaturated compound (4). Withless than 1 mole of the base, the yield of the unsaturated compoundobtained by the method of the present invention may be reduced. Althoughaddition of even a large excess amount of the base hardly affects theyield of the unsaturated compound obtainable by the manufacturing methodof the present invention, but it complicates the work-up procedure aftercompletion of the reaction. Thus, preferable amount of the base used isin the range of 1 to 5 times that of the aromatic compound (3) or theunsaturated compound (4) in moles.

The manufacturing method of the unsaturated compounds mentioned above isusually carried out in the presence of a solvent inert to the reaction.Although any solvent can be used without particular restriction so longas it does not inhibit the reaction severely, examples of such solventspreferably used include aliphatic organic solvents such as pentane,hexane, heptane, octane, etc.; alicyclic organic solvents such ascyclohexane, methylcyclohexane, etc.; aromatic organic solvents such asbenzene, toluene, xylene, etc.; ethers such as diethyl ether,diisopropyl ether, dimethoxyethane, tetrahydrofuran, dioxane, dioxolane,etc.; acetonitrile, dimethylformamide, dimethylsulfoxide,hexamethylphosphotriamide. Among them, aromatic organic solvents such asbenzene, toluene, xylene, etc., and ethers such as diethyl ether,dimethoxyethane, tetrahydrofuran, dioxane, etc. are used morepreferably.

The present invention can be carried out in an atmosphere of inert gasessuch as nitrogen, argon, etc., under normal pressure or under increasedpressure.

The present invention can be carried out at temperatures in the rangefrom about 0° C. to 300° C., or more preferably at temperatures in therange of about 20° C. to 200° C.

The reaction time of the present invention varies depending on the kindof the reaction and the reaction temperature, but can be selected from arange of about several minutes to 72 hours.

After completion of the reaction, the reaction mixture obtained istreated by the ordinary methods to give the objective compound.

Another manufacturing method of unsaturated compounds of the presentinvention is the one according to the reaction below:

Thus, an aromatic compound (3) and a carbonyl or cyano compound (14) arereacted, in the presence of a base by using the palladium-phosphinecomplex or by using palladium compound and phosphine compound of thepresent invention as catalyst to give an aromatic carbonyl or cyanocompound (15).

Examples of the (hetero)aryl compound of formula (3), which is used inthe present invention, include those similar to those mentioned above.

The compounds of formula (14) which are employable in the presentinvention are selected from the compounds which have a methylene groupare able to generate a carboanion under the influence of a base, namelyso called active-methylene compounds. Examples of such compounds includemonoketones, diketones, esters, diesters, nitriles and amides. Specificexamples of such compounds include acetone, 2-butanone, 2-pentanone,3-pentanone, acetophenone, 2,4-pentanedione, 2,4-hexanedione,1,3-cyclopentanedione, 1,3-cyclohexanedione,1,3-diphenyl-1,3-propanedione, methyl acetate, ethyl acetate, butylacetate, tert-butyl acetate, phenyl acetate, ethyl butylate, ethylisobutylate, ethyl 2-phenylacetate, diethyl succinate, γ-butyrolactone,dimethyl malonate, diethyl malonate, di-tert-butyl malonate, dimethylmethylmalonate, diethyl ethylmalonate, acetonitrile, propionitrile,butyronitrile, isobutyronitrile, malononitrile, methylmalononitrile,N,N-dimethylacetamide, N-methylacetamide, N,N-ethylacetamide,N,N-diphenylacetamide, propionamide, N-methylpropionamide,N,N-dimethylpropionamide, β-propiolactam and N-methyl-β-propiolactam,γ-butyrolactam, without being restricted specifically to those cited.

In this manufacturing method, it is only required that not less than 1mole of the compound (14) exist in the reaction system relative to thefigure m¹ of the aromatic compound (3). It is more preferable, however,for the compound (14) to exist in the reaction system in the range of 1to 2 times moles relative to the figure m¹ of compound (3), becauserecovery of the unreacted compound (14) becomes complicated,

In this manufacturing method, it is appropriate to use bases asauxiliary agents. The bases to be used can be selected from inorganicbases and/or organic bases without being restricted to specific ones.Examples of such bases include carbonates of alkali metals or alkalineearth metals such as lithium carbonate, sodium carbonate, potassiumcarbonate, rubidium carbonate, cesium carbonate, magnesium carbonate,calcium carbonate, barium carbonate, etc.; alkoxides of alkali metalssuch as sodium methoxide, sodium ethoxide, sodium phenoxide, sodiumtert-butoxide, potassium methoxide, potassium ethoxide, potassiumphenoxide, potassium tert-butoxide, lithium methoxide, lithium ethoxide,lithium phenoxide, lithium tert-butoxide, etc.; phosphates of alkalimetals such as lithium phosphate, potassium phosphate, sodium phosphate,etc.; and amines such as trimethylamine, triethylamine,triisopropylamine, tricyclohexylamine, diethylamine, diisopropylamine,etc.

The amount of the base used is preferably not less than equimolarrelative to the figure m of the aromatic compound (3) in m. With lessthan 1 mole equivalent of the base, the yield of the unsaturatedcompound obtained by the manufacturing method of the present inventionmay be reduced. Although addition of even a large excess amount of thebase hardly affect adversely the yield of the unsaturated compoundobtained by the manufacturing method of the present invention, but itcomplicates the work-up procedure after completion of the reaction.Thus, the amount of the base used is more preferably in the range from 1to 5 times in moles.

The manufacturing method of unsaturated compounds mentioned above isusually carried out in the presence of a solvent inert to the reaction.Any solvent can be used without particular limitation so long as they donot inhibit the reaction severely. Examples of such solvents includealiphatic organic solvents such as pentane, hexane, heptane, octane,etc.; alicyclic organic solvents such as cyclohexane, methylcyclohexane,etc., aromatic organic solvents such as benzene, toluene, xylene, etc.;ethers such as diethyl ether, diisopropyl ether, dimethoxyethane,tetrahydrofuran, dioxane, dioxolane, etc.; acetonitrile,dimethylformamide, dimethylsulfoxide, hexamethylphosphotriamide. Amongthem, aromatic organic solvents such as benzene, toluene, xylene, etc.,and ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran,dioxane, etc. are used more preferably.

The present invention can be carried out in an atmosphere of inert gasessuch as nitrogen or argon under normal pressure or under increasedpressure.

The present invention can be carried out at temperatures in the rangefrom about 0° C. to 300° C., or more preferably at temperatures in therange from about 20° C. to 200° C.

The reaction time of the present invention varies depending on the kindof the reaction and the reaction temperature, but can be selected from arange of about several minutes to 72 hours.

After completion of the reaction, the reaction mixture obtained istreated by the ordinary methods to give the objective compound.

Further, one of the manufacturing methods of the unsaturated compoundsof the present invention is the one according to the reaction below:

Namely, an aromatic compound (3), an alcohol (16) and carbon monoxideare reacted in the presence of a base by using the palladium-phosphinecomplex of the present invention or by using palladium compound andphosphine compound of the present invention as catalyst to give anaromatic carboxylic ester (17).

Examples of the aromatic compound (3) which can be used in thisinvention include those similar to those mentioned above. The alcoholsare those of 1-4 carbon atoms, including methanol, ethanol, n-propanol,isopropanol, n-butanol, isobutanol and sec-butanol.

In this manufacturing method, the alcohol (16) is to be present in thereaction system in an amount of a range of not less than equimolarrelative to the figure m¹ of the aromatic compound (3). However, incases where recovery of the unreacted alcohol (16) becomes complicated,it is more preferable for the alcohol to exist in the reaction system inthe range from 1 to 3 times m¹ of the aromatic compound (3) in moles.

In this manufacturing method, it is appropriate to use bases asauxiliary agents. The bases to be used can be selected from inorganicbases and/or organic bases without particular restriction. Examples ofsuch bases include carbonates of alkali metals or alkaline earth metalssuch as lithium carbonate, sodium carbonate, potassium carbonate,rubidium carbonate, cesium carbonate, magnesium carbonate, calciumcarbonate, barium carbonate, etc.; alkoxides of alkali metals such assodium methoxide, sodium ethoxide, sodium phenoxide, sodiumtert-butoxide, potassium methoxide, potassium ethoxide, potassiumphenoxide, potassium tert-butoxide, lithium methoxide, lithium ethoxide,lithium phenoxide, lithium tert-butoxide, etc.; alkali metal or alkalineearth metal hydroxides such as sodium hydroxide, potassium hydroxide,lithium hydroxide, barium hydroxide, etc.; phosphates of alkali metalssuch as lithium phosphate, potassium phosphate, sodium phosphate, etc.;and amines such as trimethylamine, triethylamine, triisopropylamine,tricyclohexylamine, diethylamine, diisopropylamine, etc.; and acetatesof alkali metals such as sodium acetate, potassium acetate, lithiumacetate, etc.

The amount of the base used is preferably not less than equimolarrelative to the figure m¹ of the aromatic compound (3). With less than 1mole equivalent of the base, the yield of the unsaturated compoundobtained by the manufacturing method of the present invention may bereduced. Although addition of even a large excess amount of the basehardly affects adversely the yield of the unsaturated compound obtainedby the manufacturing method of the present invention, it complicates thework-up procedure after completion of the reaction. Thus, the amount ofthe base used is more preferably in the range from 1 to 5 times inmoles.

The manufacturing method of unsaturated compounds mentioned above isusually carried out in the presence of a solvent inert to the reaction.Although there is no particular limitation for the solvent, any solventcan be used so long as it does not inhibit the reaction severely.Examples of such solvent include aliphatic organic solvents such aspentane, hexane, heptane, octane, etc.; alicyclic organic solvents suchas cyclohexane, methylcyclohexane, etc.; aromatic organic solvents suchas benzene, toluene, xylene, etc.; ethers such as diethyl ether,diisopropyl ether, dimethoxyethane, tetrahydrofuran, dioxane, dioxolane,etc.; acetonitrile, dimethylformamide, dimethylsulfoxide,hexamethylphosphotriamide. Among them, aromatic organic solvents such asbenzene, toluene, xylene, etc., and ethers such as diethyl ether,dimethoxyethane, tetrahydrofuran, dioxane, etc. are used morepreferably.

The present invention is usually carried out under pressure with carbonmonoxide. The pressure of the carbon monoxide used is in the range fromabout 0.1 to 30 MPa, or more preferably in the range of about 0.1 to 20MPa.

The reaction of the present invention can be carried out at temperaturesin the range from about 0° C. to 300° C., or more preferably attemperatures in a range from about 20° C. to 200° C.

The reaction time of the present invention varies depending on theindividual reaction and the reaction temperature, but can be selectedfrom a range of about several minutes to 72 hours.

After completion of the reaction, the reaction mixture is treated by theordinary methods to give the objective compound.

The palladium-phosphine complexes, which are used in the presentinvention as catalyst, can be obtained in catalytically active formseven when they are prepared by the so-called in situ method, namely byadding the palladium compound and the phosphine compound directly to thereaction system.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention will be explained in more detail with reference tothe following Examples, but the invention should not be restrictedthereby.

The apparatus used to measure each of the following physical propertiesin Examples is as follows:

-   1) ¹H-NMR spectrum: a GEMINI2000 (manufactured by Varian Inc.) or a    DRX-500 (manufactured by Bruker Co.); internal standard:    tetramethylsilane.-   2) ³¹P-NMR spectrum: a DRX-500 apparatus (manufactured by Bruker    Co.); external standard: 85 weight % phosphoric acid.-   3) Gas-chromatograph: a GC 353 (manufactured by GL Science Co.);    column: a NB-1 (30 m×0.25 mm) (manufactured by GL Science Co.);    internal standard: biphenyl.

EXAMPLE 1 Preparation of2,2-diphenyl-1-(diphenylphosphino)-1-methylcyclopropane (1) Preparationof 1,1-dibromo-2,2-diphenylcyclopropane

Under a nitrogen atmosphere, potassium tert-butoxide (14.8 g, 132 mmol),diphenylethylene (13.2 g, 73.3 mmol) and hexane (75 ml) were placed in areaction flask and cooled to −5° C. To this, bromoform (24.1 ml, 95.4mmol) was added gradually, and the mixture was stirred at the sametemperature for 30 minutes. Then, water was added to the reactionmixture and the organic layer was extracted with toluene. The tolueneextract was dried over anhydrous magnesium sulfate and then the solventwas removed under reduced pressure. The residue was recrystallized froma mixed solvent of isopropanol and toluene to give the title compound(14.4 g, 56%) as white crystal.

¹H-NMR(CDCl₃) δ2.47(s, 3H), 7.16-7.37(m, 6H), 7.46-7.57(m, 4H)

(2) Preparation of 1-bromo-2,2-diphenyl-1-methylcyclopropane

Under a nitrogen atmosphere, 1,1-dibromo-2,2-diphenylcyclopropane(10.6g, 30.0 mmol) obtained in Example 1-(1) and THF (tetrahydrofuran, 120ml) were placed in a reaction flask and cooled to −70° C. To themixture, n-butyllithium in hexane (20 ml, 1.57M, 31.4 mmol) was addedgradually, and the mixture was stirred at the same temperature for 30minutes. Methyl iodide (2.1 ml, 33 mmol) was added to the reactionmixture and the resulting mixture was stirred for 30 minutes and thenwarmed to room temperature. Then, water was added to the reactionmixture and the organic layer was extracted with toluene. The tolueneextract was dried over anhydrous magnesium sulfate and then the solventwas removed under reduced pressure. The residue was recrystallized frommethanol to give the title compound (7.28 g, 89%) as white crystal.

¹H-NMR(CDCl₃) δ1.71(d, J=6.3 Hz, 1H), 1.75(s, 3H), 1.97(d, J=6.3 Hz,1H), 7.10-7.56(m, 10H)

(3) Preparation of2,2-diphenyl-1-(diphenylphosphino)-1-methylcyclopropane

Under a nitrogen atmosphere, 1-bromo-2,2-diphenylcyclopropane (1.44 g,5.0 mmol) and magnesium (0.134 g, 5.5 mmol) and THF (10 ml) were placedin a reaction flask. Then, a trace amount of iodine was added and themixture was stirred at 40° C. for 2 hours. After cooling, copper iodide(0.961 g, 5.0 mmol) and chlorodiphenylphosphine (0.90 ml, 5.0 mmol) wereadded and the resulting mixture was stirred at 40° C. for 20 hours.After cooling to room temperature, hexane (10 ml) was added to thereaction mixture, and crystal separated was then collected byfiltration. The crystal was dissolved in toluene, washed with an aqueous28% ammonia solution and a brine, and dried over anhydrous magnesiumsulfate. The solvent was then removed under reduced pressure and theconcentrate was recrystallized from a mixture of methanol and toluene togive the title compound (0.98 g, 50%) as white crystal.

¹H-NMR(CDCl₃) δ1.08(d, J=2.6 Hz, 3H), 1.55(d/d, J=4.8, 9.7 Hz, 1H),2.12(d/d, J=4.8, 15.6 Hz, 1H), 7.08-7.59(m, 20H); ³¹P-NMR(CDCl₃) δ 8.29.

EXAMPLE 2 Preparation of2,2-diphenyl-1-(diisopropylphosphino)-1-methylcyclopropane

Under a nitrogen atmosphere, 1-bromo-2,2-diphenylcyclopropane (1.43 g,5.0 mmol), magnesium (0.133 g, 5.5 mmol) and THF (10 ml) were placed ina reaction flask, followed by addition of a trace amount of iodine andstirring at 40° C. for 1.5 hours. After cooling, copper iodide (0.952 g,5.0 mmol) and chlorodiisopropylphosphine (0.80 ml, 5.0 mmol) were addedand the resulting mixture was stirred at 40° C. for 5 hours, followed bycooling to room temperature. The resulting mixture was diluted withhexane (20 ml) and crystal separated was collected by filtration. Thecrystal was dissolved in toluene, and the toluene solution was washedwith a 28% aqueous ammonia and a brine, and dried over anhydrousmagnesium sulfate. Then, the solvent was removed under reduced pressureto give the title compound (1.06 g, 66%) as white crystal.

¹H-NMR(CDCl₃) δ 1.10-1.45(m, 16H), 2.20-2.46(m, 3H), 7.12-7.54(m, 10H);³¹P-NMR(CDCl₃) δ 22.70.

EXAMPLE 3 Preparation of2,2-diphenyl-1-(di-tert-butylphosphino)-1-methylcyclopropane

Under a nitrogen atmosphere, 1-bromo-2,2-diphenyl-cyclopropane (1.44 g,5.0 mmol), magnesium (0.134 g, 5.5 mmol) and THP (10 ml) were placed ina reaction flask, followed by addition of a trace amount of iodine andstirring at 40° C. for one hour. After cooling, copper iodide (0.962 g,5.0 mmol), lithium bromide (0.567 g, 6.5 mmol) andchlorodi-tert-butylphosphine (0.95 ml, 5.0 mmol) were added and theresulting mixture was stirred at 60° C. for 3 hours, followed by coolingto room temperature. The resulting mixture was diluted with hexane (20ml) and crystal separated was collected by filtration. The crystal wasdissolved in toluene, and the toluene solution was washed with a 28%aqueous ammonia and a brine, and dried over anhydrous magnesium sulfate.The solvent was then removed under reduced pressure to give the titlecompound (0.83 g, 47%) as white crystal.

¹H-NMR(CDCl₃) δ 1.22(d, J=11.0 Hz, 9H), 1.23-1.39(m, 1H), 1.31(d, J=10.6Hz, 9H), 1.36(d, J=1.2 Hz, 3H), 2.27(d/d, J=5.0, 12.6 Hz, 1H),7.00-7.49(m, 10H); ³¹P-NMR(CDCl₃) δ 39.25.

EXAMPLE 4 Preparation of2,2-diphenyl-1-(di-tert-butylphosphino)-1-methylcyclopropane (1)Preparation of 1-chloro-1-methyl-2,2-diphenyl-cyclopropane

Under a nitrogen atmosphere, 1,1-dichloroethane (30.0 g, 303 mmol),diphenylethylene (5.59 g, 31.0 mmol) and diethyl ether (62 ml) wereplaced in a reaction flask and cooled to −40° C. To the mixture,n-butyllithium in hexane (45 ml, 1.56M, 70.2 mmol) was added graduallyand the mixture was stirred at the same temperature for one hour,followed by warming to room temperature. Then, water was added to thereaction mixture and the organic layer was extracted with toluene. Thetoluene extract was dried over anhydrous magnesium sulfate and then thesolvent was removed under reduced pressure. The concentrate wasrecrystallized from ethanol to give the title compound (5.91 g, 78%) aswhite crystal.

¹H-NMR(CDCl₃) δ 1.57(s, 3H), 1.67(d, J=6.2 Hz, 1H), 1.87(d, J=6.2 Hz,1H), 7.10-7.33(m, 6H), 7.37-7.55(m, 4H).

(2) Preparation of2,2-diphenyl-1-(di-tert-butyl-phosphino)-1-methylcyclopropane

Under a nitrogen atmosphere, 1-chloro-1-methyl-2,2-diphenylcyclopropane(2.43 g, 10.0 mmol), magnesium (0.279 g, 11.5 mmol) and THF (10 ml) wereplaced in a reaction flask, followed by addition of a trace amount ofiodine and stirring at 60° C. for 5 hours. After cooling, copper iodide(1.92 g, 10.0 mmol), lithium bromide (0.879 g, 10.1 mmol) andchlorodi-tert-butylphosphine (2.1 ml, 11.0 mmol) were added and theresulting mixture was stirred at 60° C. for 3 hours, followed by coolingto room temperature. The resulting mixture was diluted with hexane (20ml) and crystal separated was collected by filtration. The crystal wasdissolved in toluene, and the toluene solution was washed with a 28%(w/w) aqueous ammonia and a brine, and dried over anhydrous magnesiumsulfate. The solvent was removed under reduced pressure to give thetitle compound (0.89 g, 25%) as white crystal.

EXAMPLE 5 Preparation of diphenyl(4-methoxyphenyl)amine

Under a nitrogen atmosphere, diphenylamine (0.85 g, 5.0 mmol), andbiphenyl as an internal standard were placed in a reaction flask,followed by addition of 10 ml of toluene. To the mixture were addedsodium tert-butoxide (0.58 g, 6.0 mmol), 4-bromoanisole (0.69 ml, 5.5mmol), palladium acetate (2.8 mg, 0.0125 mmol) and2,2-diphenyl-1-(di-tert-butylphosphino)-1-methylcyclopropane (8.8 mg,0.025 mmol) obtained in Example 4 and the resulting mixture was stirredat 100° C. for 3 hours. The reaction mixture was cooled and analyzed gaschromatography to reveal the formation of the objectivediphenyl(4-methoxyphenyl)amine in a yield of 95%.

¹H-NMR(CDCl₃) δ 3.80(s, 3H), 6.79-7.28(m, 14H)

EXAMPLE 6 Preparation of diphenyl(4-methoxyphenyl)amine

To a solution of diphenylamine (0.34 g, 2.0 mmol) in 4 ml of toluenewere added sodium tert-butoxide (0.23 g, 2.4 mmol), 4-chloroanisole(0.27 ml, 2.2 mmol), (π-allyl)palladium chloride (3.7 mg, 0.01 mmol) and2,2-diphenyl-1-(di-tert-butylphosphino)-1-methylcyclopropane (14.1 mg,0.04 mmol) obtained in Example 4 under a nitrogen atmosphere and themixture was stirred for 3 hours at 100° C. The reaction mixture wascooled, washed with water, and dried over anhydrous magnesium sulfate.Then, the solvent was removed under reduced pressure, and theconcentrate was purified by column chromatography to give the titlecompound (0.53 g, 95%) as white crystal.

EXAMPLE 7 Preparation of N-phenylcarbazole

To a solution of carbazole (0.34 g, 2.0 mmol) in xylene (4 ml) wereadded sodium tert-butoxide (0.23 g, 2.4 mmol), bromobenzene (0.23 ml,2.2 mmol), palladium acetate (4.5 mg, 0.02 mmol) and2,2-diphenyl-1-(di-tert-butylphosphino)-1-methylcyclopropane (14.1 mg,0.04 mmol) obtained in Example 4 under a nitrogen atmosphere and themixture was stirred for 3 hours at 120° C. The reaction mixture wascooled, washed with water, and dried over anhydrous magnesium sulfate.Then, the solvent was removed under reduced pressure, and theconcentrate was purified by column chromatography to giveN-phenylcarbazole (0.479 g, 98%, purity: >99%) as white crystal.

¹H-NMR(CDCl₃) δ7.23-7.67(m, 11H), 8.15(br-d, J=7.6 Hz, 2H).

EXAMPLE 8 Preparation of 4-methoxybiphenyl

Under a nitrogen atmosphere, 4-trifluoromethane-sulfonyloxyanisole (0.49g, 1.9 mmol), phenylboronic acid (0.29 g, 2.4 mmol), potassium fluoride(0.24 g, 4.2 mmol), (π-allyl)palladium chloride (3.6 mg, 0.01 mmol),2,2-diphenyl-1-(di-tert-butylphosphino)-1-methylcyclopropane (14.0 mg,0.04 mmol) obtained in Example 4 and toluene (4 ml) were placed in areaction flask and stirred for 1.5 hours at 80° C. The reaction mixturewas cooled, washed with water, and dried over anhydrous magnesiumsulfate. Then, the solvent was removed under reduced pressure, and theconcentrate was purified by column chromatography to give the titlecompound (0.34 g, 96%) as white crystal.

¹H-NMR(CDCl₃) δ3.85(s, 3H), 6.93-7.04(m, 2H), 7.23-7.69(m, 7H).

EXAMPLE 9 Preparation of 4-methoxybiphenyl

Under a nitrogen atmosphere, 4-chloroanisole (0.30 g, 2.1 mmol),phenylboronic acid (0.37 g, 3.0 mmol), potassium phosphate n-hydrate(0.85 g), (π-allyl)palladium chloride (3.7 mg, 0.01 mmol),2,2-diphenyl-1-(di-tert-butylphosphino)-1-methylcyclopropane (14.1 mg,0.04 mmol) obtained in Example 4 and toluene (4 ml) were placed in areaction flask and stirred for 3 hours at 80° C. The reaction mixturewas cooled, washed with water, and dried over anhydrous magnesiumsulfate. Then, the solvent was removed under reduced pressure, and theconcentrate was purified by column chromatography to give the titlecompound (0.35 g, 90%) as white crystal.

EXAMPLE 10 Preparation of[2,2-diphenyl-1-(d-tert-butylphosphino)-1-methylcyclopropane](π-allyl)palladiumchloride

Under a nitrogen atmosphere, (π-allyl)palladium chloride dimer (0.183 g,0.5 mmol), 2,2-diphenyl-1-(di-tert-butyl-phosphino)-1-methylcyclopropane(0.352, 1.0 mmol) and 3 ml of toluene were placed in a reaction flaskand the mixture was stirred at room temperature for 6 hours. Crystalseparated was filtered and dried to give the title compound (0.490 g,91%).

¹H-NMR(CDCl₃) δ 1.01-1.16(m, 1H), 1.34-1.71(m, 10H), 1.43(d, J=5.2 Hz,3H), 1.47(d, J=12.8 Hz, OH), 2.28-3.10(m, 1H), 3.35(br-s, 1H),3.96(br-d, J=16.4 Hz, 1H), 4.35(br-s, 1H), 5.26(br-s, 1H), 6.92-7.06(m,1H), 7.08-7.47(m, 7H), 7.68-7.84(m, 2H); ³¹P-NMR(CDCl₃) δ 75.63.

INDUSTRIAL APPLICABILITY

The phosphine compounds of the present invention form, with palladiumcompounds, palladium-phosphine complexes which show high efficiency ascatalyst for the coupling reactions of unsaturated compounds andaromatic compounds.

1. A phosphine compound of formula (1),

wherein R¹ is a hydrogen atom, an alkyl group, a cycloalkyl group or aphenyl group which may be substituted; R² and R³ are each, the same ordifferent, an alkyl group, a cycloalkyl group or a phenyl group whichmay be substituted; R⁴ and R⁵ are each, the same or different, ahydrogen atom, an alkyl group, a cycloalkyl group or a phenyl groupwhich may be substituted; R⁶, R⁷, R⁸ and R⁹ are each, the same ordifferent, an alkyl group, a cycloalkyl group, a phenyl group which maybe substituted, an alkoxyl group, a dialkylamino group, a halogen atom,a benzyl group, a naphthyl group or a halogenated alkyl group; R⁶ andR⁷, or R⁸ and R⁹ each may be combined to form, a fused ring, atrimethylene group, a tetramethylene group or a methylenedioxy group; p,q, r and s are each an integer of from 0 to 5; and p+q, and r+s are eachin the range of from 0 to
 5. 2. A palladium-phosphine complex which canbe obtained by reacting the phosphine compound of claim 1 with apalladium compound.
 3. The palladium-phosphine complex of claim 2,wherein the palladium compound is a palladium salt or a palladiumcomplex in which the valency of palladium is 4, 2 or
 0. 4. Amanufacturing method of an unsaturated compound or an aromatic compoundby the use of palladium-phosphine complexes mentioned in claim 2 as acatalyst.
 5. A manufacturing method of an unsaturated compound or anaromatic compound by the use of the phosphine compound mentioned inclaim 1 and a palladium compound.
 6. The manufacturing method of claim 4or 5, which comprises reacting a compound of formula (3) or (4) below:

wherein, in formula (3), Ar¹ is an aryl group which may be substitutedor a heteroaryl group which may be substituted; X¹ is a chlorine atom, abromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, amethanesulfonyloxy group or a para-toluenesulfonyloxy group and m¹ is aninteger of 1 to 4, and, in formula (4), R¹⁰¹, R¹¹¹ and R¹²¹ are each,the same or different, a hydrogen atom, an alkyl group, an aryl groupwhich may be substituted, a heteroaryl group which may be substituted,an alkoxycarbonyl group or a cyano group; X¹¹ is a chlorine atom, abromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, amethanesulfonyloxy group or a para-toluenesulfonyloxy group, with acompound, of formula (5) or (6) below,

wherein, in formula (5), Ar² is an aryl group which may be substitutedor a heteroaryl group which may be substituted; X² is B(OR¹³)(OR¹⁴),Sn(R¹⁵)₃, MgX, ZnX, Al(R¹⁵)₂ or Li, and, in formula (6), R¹⁰, R¹¹ andR¹² are each, the same or different, a hydrogen atom, an alkyl group, anaryl group which may be substituted, a heteroaryl group which may besubstituted, an alkoxycarbonyl group or a cyano group; R¹⁰ and R¹² maybe combined to form a single bond, forming together with the existingdouble bond a triple bond; X³ is a hydrogen atom, B(OR¹³)(OR¹⁴),Sn(R¹⁵)₃, MgX, ZnX, Al(R¹⁵)₂ or Li; R¹³ and R¹⁴ are each, the same ordifferent, a hydrogen atom, an alkyl group, or, combined to form anethylene group or a 1,2-dimethylethylene group; R¹⁵ is an alkyl group,and X is a chlorine atom, a bromine atom or an iodine atom, to give acompound of formula (7), (8), (9) or (10),

wherein Ar¹, Ar², R¹⁰, R¹¹, R¹², R¹⁰¹, R¹¹¹ and R¹²¹ are as definedabove and m² is an integer of 1 to
 4. 7. A manufacturing method of claim4, which comprises reacting a compound of formula (3) or (4) below,

wherein, in formula (3), Ar¹ is an aryl group which may be substitutedor a heteroaryl group which may be substituted; X¹ is a chlorine atom, abromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, amethanesulfonyloxy group or a para-toluenesulfonyloxy group and m¹ is aninteger of from 1 to 4, and, in formula (4), R¹⁰¹, R¹¹¹ and R¹²¹ areeach, the same or different, a hydrogen atom, an alkyl group, an arylgroup which may be substituted, a heteroaryl group which may besubstituted, an alkoxycarbonyl group or a cyano group; X¹¹ is a chlorineatom, a bromine atom, an iodine atom, a trifluoromethanesulfonyloxygroup, a methanesulfonyloxy group or a para-toluenesulfonyloxy group,with an oxygen compound or a nitrogen compound of formula (11) below,R¹⁶-QH  (11) wherein R¹⁶ is an alkyl group, an aryl group which may besubstituted or a heteroaryl group which may be substituted; Q is anoxygen atom,

wherein R¹⁷, R¹⁸ and R¹⁹ are each a hydrogen atom, an alkyl group, anaryl group which may be substituted or a heteroaryl group which may besubstituted; and R¹⁶ and R¹⁷ may be combined to form a divalent aromaticring which may be substituted, to give a compound of formula (12) or(13) below,

wherein Ar¹, Q, R¹⁶, R¹⁰¹, R¹¹¹ and R¹²¹ are as defined above and m³ isan integer of 1 to
 4. 8. The manufacturing method of claim 4, whichcomprises reacting an aromatic compound of formula (3),Ar¹(X¹)_(m) ¹  (3) wherein Ar¹ is an aryl group which may be substitutedor a heteroaryl group which may be substituted; X¹ is a chlorine atom, abromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, amethanesulfonyloxy group or a para-toluenesulfonyloxy group, and m¹ isan integer of from 1 to 4, with a carbonyl compound or a cyano compoundof formula (14),R¹⁸—CH₂—R¹⁹  (14) wherein R¹⁸ is a hydrogen atom, CO₂R²⁰, C(═O)R²¹ or acyano group; R¹⁹ is CO₂R²², C(═O)R²³ or a cyano group; R²⁰, R²¹, R²² andR²³ are each an alkyl group, an aryl group which may be substituted or aheteroaryl group which may be substituted, to give a compound of formula(15),

wherein Ar¹, R¹⁸ and R¹⁹ are as defined above and m⁴ is an integer of 1to
 4. 9. The manufacturing method of claim 4, which comprises reactingan aromatic compound of formula (3),Ar¹(X¹)_(m) ¹  (3) wherein Ar¹ is an aryl group which may be substitutedor a heteroaryl group which may be substituted; X¹ is a chlorine atom, abromine atom, an iodine atom, a trifluoromethanesulfonyloxy group, amethanesulfonyloxy group or a para-toluenesulfonyloxy group; and m¹ isan integer of from 1 to 4, with carbon monoxide and an alcohol offormula (16),R²⁴OH  (16) wherein R²⁴ is an alkyl group, to give a carboxylic ester offormula (17),Ar¹(CO₂R²⁴)m⁵  (17) wherein Ar¹ and R²⁴ are as defined above and m⁵ isan integer of 1 to
 4. 10. The manufacturing method of unsaturatedcompounds, as claimed in claim 4, which comprises carrying out thereaction in the presence of a base.
 11. A halogeno compound of formula(2) below,

wherein R¹, R⁴ and R⁵ are each, the same or different, a hydrogen atom,an alkyl group, a cycloalkyl group or a phenyl group which may besubstituted; X⁴ is a halogen atom; R⁶, R⁷, R⁸ and R⁹ are each, the sameor different, an alkyl group, a cycloalkyl group or a phenyl group whichmay be substituted, an alkoxy group, a dialkylamino group, a halogenatom, a phenyl group, a benzyl group, a naphthyl group or a halogenatedalkyl group; R⁶ and R⁷, and R⁸ and R⁹ each may be combined to form afused ring, a trimethylene group, a tetramethylene group or amethylenedioxy group; p, q, r and s are each an integer of from 0 to 5;and p+q and r+s are each in the range of from 0 to 5.